Skip to main content
SpringerLink
Log in
Book cover

Interleukin-10 in Health and Disease pp 1–18Cite as

IL-10 in Humans: Lessons from the Gut, IL-10/IL-10 Receptor Deficiencies, and IL-10 Polymorphisms

  • Chapter
  • First Online:

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 380))

Abstract

Inflammatory bowel disease (IBD) represents a heterogeneous group of gastrointestinal disorders, where commensal gut flora provokes an either (a) insufficient or (b) uncontrolled immune response. This results either in a lack of or in excessive inflammation mainly manifesting as Crohn’s disease or ulcerative colitis. IBD commonly presents in adolescence and adulthood and often follows a chronic relapsing course. Genetic and/or environmental factors contribute to the failure of gut immune homeostasis. Genome-wide association studies have identified over 160 susceptibility loci associated with IBD, including polymorphisms in interleukin-10 (IL-10). The anti-inflammatory cytokine IL-10 dampens intestinal inflammation and is therefore a good candidate gene for IBD. Polymorphisms in the IL-10 receptor are also associated with ulcerative colitis presenting in early childhood. Moreover, severe infantile enterocolitis resembling Crohn’s disease, caused by loss-of-function mutations in IL-10 and IL-10 receptor, is characterised by a very early onset (usually within the first 3 months of life), unresponsiveness to standard treatment including immunosuppressive therapy, and severe perianal disease with abscesses and fistulas. In these patients, inflammation and polymorphic infiltrates are mainly confined to the colon with very little involvement of the small intestine. Ulceration and granulomas, bloody diarrhoea and failure to thrive also occur. Furthermore, patients may suffer from recurrent fever and respiratory infections. Individuals with IL-10 receptor mutations also experience cutaneous folliculitis and arthritis. Hematopoietic stem cell transplantation is currently the only curative therapy.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Abraham C, Cho JH (2009) Inflammatory bowel disease. N Engl J Med 361:2066–2078. doi:10.1056/NEJMra0804647

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bäckhed F, Ley RE, Sonnenburg JL, Peterson DA, Gordon JI (2005) Host-bacterial mutualism in the human intestine. Science 307:1915–1920

    Article  PubMed  Google Scholar 

  • Barnes MJ, Powrie F (2009) Regulatory T cells reinforce intestinal homeostasis. Immunity 31:401–411. doi:10.1016/j.immuni.2009.08.011

    Article  CAS  PubMed  Google Scholar 

  • Barrett JC, Hansoul S, Nicolae DL, Cho JH, Duerr RH, Rioux JD et al (2008) Genome-wide association defines more than 30 distinct susceptibility loci for Crohn’s disease. Nat Genet 40:955–962. doi:10.1038/ng.175

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Baumgart DC, Carding SR (2007) Inflammatory bowel disease: cause and immunobiology. Lancet 369:1627–1640

    Article  CAS  PubMed  Google Scholar 

  • Begue B, Verdier J, Rieux-Laucat F, Goulet O, Morali A, Canioni D et al (2011) Defective IL-10 signaling defining a subgroup of patients with inflammatory bowel disease. Am J Gastroenterol 106:1544–1555. doi:10.1038/ajg.2011.112

    Article  CAS  PubMed  Google Scholar 

  • Braat H, Rottiers P, Hommes DW, Huyghebaert N, Remaut E, Remon JP et al (2006) A phase I trial with transgenic bacteria expressing interleukin-10 in Crohn’s disease. Clin Gastroenterol Hepatol 4:754–759

    Article  CAS  PubMed  Google Scholar 

  • Chaudhry A, Samstein RM, Treuting P, Liang Y, Pils MC, Heinrich JM et al (2011) Interleukin-10 signaling in regulatory T cells is required for suppression of th17 cell-mediated inflammation. Immunity 34:566–578. doi:10.1016/j.immuni.2011.03.018

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Cheng LE, Kanwar B, Tcheurekdjian H, Grenert JP, Muskat M, Heyman MB et al (2009) Persistent systemic inflammation and atypical enterocolitis in patients with NEMO syndrome. Clin Immunol 132:124–131. doi:10.1016/j.clim.2009.03.514

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Cho JH (2008) The genetics and immunopathogenesis of inflammatory bowel disease. Nat Rev Immunol 8:458–466. doi:10.1038/nri2340

    Article  CAS  PubMed  Google Scholar 

  • Commins S, Steinke JW, Borish L (2008) The extended IL-10 superfamily: IL-10, IL-19, IL-20, IL-22, IL-24, IL-26, IL-28, and IL-29. J Allergy Clin Immunol 121:1108–1111. doi:10.1016/j.jaci.2008.02.026

    Article  CAS  PubMed  Google Scholar 

  • Donnelly RP, Dickensheets H, Finbloom DS (1999) The interleukin-10 signal transduction pathway and regulation of gene expression in mononuclear phagocytes. J Interferon Cytokine Res 19:563–573

    Article  CAS  PubMed  Google Scholar 

  • Donnelly RP, Sheikh F, Kotenko SV, Dickensheets H (2004) The expanded family of class II cytokines that share the IL-10 receptor-2 (IL-10R2) chain. J Leukoc Biol 76:314–321

    Article  CAS  PubMed  Google Scholar 

  • Elson CO, Cong Y, McCracken VJ, Dimmitt RA, Lorenz RG, Weaver CT (2005) Experimental models of inflammatory bowel disease reveal innate, adaptive, and regulatory mechanisms of host dialogue with the microbiota. Immunol Rev 206:60–76

    Article  Google Scholar 

  • Elson CO, Cong Y, Weaver CT, Schoeb TR, McClanahan TK, Fick RB, Kastelein RA (2007) Monoclonal anti-interleukin 23 reverses active colitis in a T cell-mediated model in mice. Gastroenterology 132:2359–2370

    Article  CAS  PubMed  Google Scholar 

  • Engel MA, Neurath MF (2010) New pathophysiological insights and modern treatment of IBD. J Gastroenterol 45:571–583. doi:10.1007/s00535-010-0219-3

    Article  CAS  PubMed  Google Scholar 

  • Engelhardt KR, Shah N, Faizura-Yeop I, Kocacik Uygun DF, Frede N, Muise AM et al (2013) Clinical outcome in IL-10- and IL-10 receptor-deficient patients with or without hematopoietic stem cell transplantation. J Allergy Clin Immunol 131:825–830. doi:10.1016/j.jaci.2012.09.025

    Article  CAS  PubMed  Google Scholar 

  • Fava F, Danese S (2011) Intestinal microbiota in inflammatory bowel disease: friend or foe? World J Gastroenterol 17:557–566. doi:10.3748/wjg.v17.i5.557

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Fiorentino DF, Zlotnik A, Mosmann TR, Howard M, O’Garra A (1991a) IL-10 inhibits cytokine production by activated macrophages. J Immunol 147:3815–3822

    CAS  PubMed  Google Scholar 

  • Fiorentino DF, Zlotnik A, Vieira P, Mosmann TR, Howard M, Moore KW, O’Garra A (1991b) IL-10 acts on the antigen-presenting cell to inhibit cytokine production by Th1 cells. J Immunol 146:3444–3451

    CAS  PubMed  Google Scholar 

  • Franke A, Balschun T, Karlsen TH, Hedderich J, May S, Lu T et al (2008a) Replication of signals from recent studies of Crohn’s disease identifies previously unknown disease loci for ulcerative colitis. Nat Genet 40:713–715. doi:10.1038/ng.(a)

    Article  CAS  PubMed  Google Scholar 

  • Franke A, Balschun T, Karlsen TH, Sventoraityte J, Nikolaus S, Mayr G et al (2008b) Sequence variants in IL10, ARPC2 and multiple other loci contribute to ulcerative colitis susceptibility. Nat Genet 40:1319–1323. doi:10.1038/ng.221.(b)

    Article  CAS  PubMed  Google Scholar 

  • Franke A, McGovern DP, Barrett JC, Wang K, Radford-Smith GL, Ahmad T et al (2010) Genome-wide meta-analysis increases to 71 the number of confirmed Crohn’s disease susceptibility loci. Nat Genet 42:1118–1125. doi:10.1038/ng.717

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Glocker EO, Kotlarz D, Boztug K, Gertz EM, Schäffer AA, Noyan F et al (2009) Inflammatory bowel disease and mutations affecting the Interleukin-10 Receptor. N Engl J Med 361:2033–2045. doi:10.1056/NEJMoa0907206

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Glocker EO, Frede N, Perro M, Sebire N, Elawad M, Shah N et al (2010) Infant colitis—it’s in the genes. Lancet 376:1272. doi:10.1016/S0140-6736(10)61008-2

    Article  PubMed  Google Scholar 

  • Goyette P, Labbé C, Trinh TT, Xavier RJ, Rioux JD (2007) Molecular pathogenesis of inflammatory bowel disease: genotypes, phenotypes and personalized medicine. Ann Med 39:177–199

    Article  CAS  PubMed  Google Scholar 

  • Hampe J, Franke A, Rosenstiel P, Till A, Teuber M, Huse K et al (2007) A genome-wide association scan of non-synonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1. Nat Genet 39:207–211

    Article  CAS  PubMed  Google Scholar 

  • Holland SM, DeLeo FR, Elloumi HZ, Hsu AP, Uzel G, Brodsky N et al (2007) STAT3 mutations in the hyper-IgE syndrome. N Engl J Med 357:1608–1619

    Article  CAS  PubMed  Google Scholar 

  • Huber S, Gagliani N, Esplugues E, O’Connor W Jr, Huber FJ, Chaudhry A et al (2011) Th17 cells express interleukin-10 receptor and are controlled by Foxp3(−) and Foxp3(+) regulatory CD4(+) T cells in an interleukin-10-dependent manner. Immunity 34:554–565. doi:10.1016/j.immuni.2011.01.020

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hugot JP, Chamaillard M, Zouali H, Lesage S, Cézard JP, Belaiche J et al (2001) Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn’s disease. Nature 411:599–603

    Article  CAS  PubMed  Google Scholar 

  • Imielinski M, Baldassano RN, Griffiths A, Russell RK, Annese V, Dubinsky M et al (2009) Common variants at five new loci associated with early-onset inflammatory bowel disease. Nat Genet 41:1335–1340. doi:10.1038/ng.489

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ito T, Yang M, Wang YH, Lande R, Gregorio J, Perng OA et al (2007) Plasmacytoid dendritic cells prime IL-10-producing T regulatory cells by inducible costimulator ligand. J Exp Med 204:105–115

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Izcue A, Coombes JL, Powrie F (2006) Regulatory T cells suppress systemic and mucosal immune activation to control intestinal inflammation. Immunol Rev 212:256–271

    Article  CAS  PubMed  Google Scholar 

  • Jostins L, Ripke S, Weersma RK, Duerr RH, McGovern DP, Hui KY et al (2012) Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 491:119–124. doi:10.1038/nature11582

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kaser A, Lee AH, Franke A, Glickman JN, Zeissig S, Tilg H et al (2008) XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease. Cell 134:743–756. doi:10.1016/j.cell.2008.07.021

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kaser A, Flak MB, Tomczak MF, Blumberg RS (2011) The unfolded protein response and its role in intestinal homeostasis and inflammation. Exp Cell Res 317:2772–2779. doi:10.1016/j.yexcr.2011.07.008

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kotenko SV, Krause CD, Izotova LS, Pollack BP, Wu W, Pestka S (1997) Identification and functional characterization of a second chain of the interleukin-10 receptor complex. EMBO J 16:5894–5903

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kotenko SV, Gallagher G, Baurin VV, Lewis-Antes A, Shen M, Shah NK et al (2003) IFN-lambdas mediate antiviral protection through a distinct class II cytokine receptor complex. Nat Immunol 4:69–77

    Article  CAS  PubMed  Google Scholar 

  • Kotlarz D, Beier R, Murugan D, Diestelhorst J, Jensen O, Boztug K et al (2012) Loss of interleukin-10 signaling and infantile inflammatory bowel disease—implications for diagnosis and therapy. Gastroenterology 143:347–355. doi:10.1053/j.gastro.2012.04.045

    Article  CAS  PubMed  Google Scholar 

  • Kühn R, Löhler J, Rennick D, Rajewsky K, Müller W (1993) Interleukin-10-deficient mice develop chronic enterocolitis. Cell 75:263–274

    Article  PubMed  Google Scholar 

  • Levine A, Griffiths A, Markowitz J, Wilson DC, Turner D, Russell RK et al (2011) Pediatric modification of the Montreal classification for inflammatory bowel disease: the Paris classification. Inflamm Bowel Dis 17:1314–1321. doi:10.1002/ibd.21493

    Article  PubMed  Google Scholar 

  • Liu Y, Wei SH, Ho AS, de Waal R, Malefyt, Moore KW (1994) Expression cloning and characterization of a human IL-10 receptor. J Immunol 152:1821–1829

    Google Scholar 

  • Makita S, Kanai T, Oshima S, Uraushihara K, Totsuka T, Sawada T et al (2004) CD4 + CD25bright T cells in human intestinal lamina propria as regulatory cells. J Immunol 173:3119–3130

    Article  CAS  PubMed  Google Scholar 

  • Mao H, Yang W, Lee PP, Ho MH, Yang J, Zeng S et al (2012) Exome sequencing identifies novel compound heterozygous mutations of IL-10 receptor 1 in neonatal-onset Crohn’s disease. Genes Immun 13:437–442. doi:10.1038/gene.2012.8

    Article  CAS  PubMed  Google Scholar 

  • Marks DJ, Segal AW (2008) Innate immunity in inflammatory bowel disease: a disease hypothesis. J Pathol 214:260–266

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Marks DJ, Miyagi K, Rahman FZ, Novelli M, Bloom SL, Segal AW (2009) Inflammatory bowel disease in CGD reproduces the clinicopathological features of Crohn’s disease. Am J Gastroenterol 104:117–124. doi:10.1038/ajg.2008.72

    Article  CAS  PubMed  Google Scholar 

  • Maxwell JR, Viney JL (2009) Overview of mouse models of inflammatory bowel disease and their use in drug discovery. Curr Protoc Pharmacol Chapter 5: Unit5.57. doi: 10.1002/0471141755.ph0557s47

  • Maynard CL, Harrington LE, Janowski KM, Oliver JR, Zindl CL, Rudensky AY, Weaver CT (2007) Regulatory T cells expressing interleukin 10 develop from Foxp3 + and Foxp3-precursor cells in the absence of interleukin 10. Nat Immunol 8:931–941

    Article  CAS  PubMed  Google Scholar 

  • Mizoguchi A, Mizoguchi E (2008) Inflammatory bowel disease, past, present, and future: lessons from animal models. J Gastroenterol 43:1–17. doi:10.1007/s00535-007-2111-3

    Article  PubMed  Google Scholar 

  • Moore KW, O’Garra A, de Waal Malefyt R, Vieira P, Mosmann TR (1993) Interleukin-10. Annu Rev Immunol 11:165–90

    Google Scholar 

  • Moore KW, de Waal Malefyt R, Coffman RL, O’Garra A (2001) Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 19:683–765

    Article  CAS  PubMed  Google Scholar 

  • Moraes-Vasconcelos D, Costa-Carvalho BT, Torgerson TR, Ochs HD (2008) Primary immune deficiency disorders presenting as autoimmune diseases: IPEX and APECED. J Clin Immunol 28(Suppl 1):S11–S19. doi:10.1007/s10875-008-9176-5

    Article  CAS  PubMed  Google Scholar 

  • Moran CJ, Walters TD, Guo CH, Kugathasan S, Klein C, Turner D et al (2013) IL10R polymorphisms are associated with very-early-onset ulcerative colitis. Inflamm Bowel Dis 19:115–123

    Article  PubMed Central  PubMed  Google Scholar 

  • Murai M, Turovskaya O, Kim G, Madan R, Karp CL, Cheroutre H et al (2009) Interleukin 10 acts on regulatory T cells to maintain expression of the transcription factor Foxp3 and suppressive function in mice with colitis. Nat Immunol 10:1178–1184. doi:10.1038/ni.1791

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Neirynck S, Steidler L (2006) Delivery of therapeutic proteins through Lactococcus lactis. Biotechnol Genet Eng Rev 22:253–266

    Article  CAS  PubMed  Google Scholar 

  • Neufert C, Pickert G, Zheng Y, Wittkopf N, Warntjen M, Nikolaev A et al (2010) Activation of epithelial STAT3 regulates intestinal homeostasis. Cell Cycle 9:652–655

    Article  CAS  PubMed  Google Scholar 

  • Neuman MG, Nanau RM (2012) Inflammatory bowel disease: role of diet, microbiota, life style. Transl Res 160:29–44. doi:10.1016/j.trsl.2011.09.001

    Article  PubMed  Google Scholar 

  • Ng SC, Woodrow S, Patel N, Subhani J, Harbord M (2012) Role of genetic and environmental factors in British twins with inflammatory bowel disease. Inflamm Bowel Dis 18:725–736. doi:10.1002/ibd.21747

    Article  PubMed  Google Scholar 

  • O’Garra A, Murphy KM (2009) From IL-10 to IL-12: how pathogens and their products stimulate APCs to induce T(H)1 development. Nat Immunol 10(9):929–932. doi:10.1038/ni0909-929

    Article  PubMed  Google Scholar 

  • Pachlopnik Schmid J, Canioni D, Moshous D, Touzot F, Mahlaoui N, Hauck F et al (2011) Clinical similarities and differences of patients with X-linked lymphoproliferative syndrome type 1 (XLP-1/SAP deficiency) vs type 2 (XLP-2/XIAP deficiency). Blood 117:1522–1529. doi:10.1182/blood-2010-07-298372

    Article  PubMed  Google Scholar 

  • Parkes M, Barrett JC, Prescott NJ, Tremelling M, Anderson CA, Fisher SA et al (2007) Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn’s disease susceptibility. Nat Genet 39:830–832

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Pestka S, Krause CD, Sarkar D, Walter MR, Shi Y, Fisher PB (2004) Interleukin-10 and related cytokines and receptors. Annu Rev Immunol 22:929–979

    Article  CAS  PubMed  Google Scholar 

  • Podolsky DK (2002) Inflammatory bowel disease. N Engl J Med 347:417–429

    Article  CAS  PubMed  Google Scholar 

  • Rioux JD, Xavier RJ, Taylor KD, Silverberg MS, Goyette P, Huett A et al (2007) Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nat Genet 39:596–604

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Sanchez R, Levy E, Costea F, Sinnett D (2009) IL-10 and TNF-alpha promoter haplotypes are associated with childhood Crohn’s disease location. World J Gastroenterol 15:3776–3782

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Satsangi J, Jewell DP, Rosenberg WM, Bell JI (1994) Genetics of inflammatory bowel disease. Gut 35:696–700

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Sawczenko A, Sandhu BK (2003) Presenting features of inflammatory bowel disease in Great Britain and Ireland. Arch Dis Child 88:995–1000

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Segal BH, Veys P, Malech H, Cowan MJ (2011) Chronic granulomatous disease: lessons from a rare disorder. Biol Blood Marrow Transplant 17(1 Suppl):S123–S131. doi:10.1016/j.bbmt.2010.09.008

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Spencer SD, Di Marco F, Hooley J, Pitts-Meek S, Bauer M, Ryan AM et al (1998) The orphan receptor CRF2-4 is an essential subunit of the interleukin 10 receptor. J Exp Med 187:571–578

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Stoll M, Corneliussen B, Costello CM, Waetzig GH, Mellgard B, Koch WA et al (2004) Genetic variation in DLG5 is associated with inflammatory bowel disease. Nat Genet 36:476–480

    Article  CAS  PubMed  Google Scholar 

  • Taupin D, Podolsky DK (2003) Trefoil factors: initiators of mucosal healing. Nat Rev Mol Cell Biol 4:721–732

    Article  CAS  PubMed  Google Scholar 

  • Thrasher AJ, Burns SO (2010) WASP: a key immunological multitasker. Nat Rev Immunol 10:182–192. doi:10.1038/nri2724

    Article  CAS  PubMed  Google Scholar 

  • Torgerson TR, Ochs HD (2007) Immune dysregulation, polyendocrinopathy, enteropathy, X-linked: forkhead box protein 3 mutations and lack of regulatory T cells. J Allergy Clin Immunol 120:744–750

    Article  CAS  PubMed  Google Scholar 

  • Turner JR (2006) Molecular basis of epithelial barrier regulation: from basic mechanisms to clinical application. Am J Pathol 169:1901–1909

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Uhlig HH, Powrie F (2005) The role of mucosal T lymphocytes in regulating intestinal inflammation. Springer Semin Immunopathol 27:167–180

    Article  PubMed  Google Scholar 

  • Van Limbergen J, Wilson DC, Satsangi J (2009) The genetics of Crohn’s disease. Annu Rev Genomics Hum Genet 10:89–116. doi:10.1146/annurev-genom-082908-150013

    Article  PubMed  Google Scholar 

  • Weber-Nordt RM, Riley JK, Greenlund AC, Moore KW, Darnell JE, Schreiber RD (1996) Stat3 recruitment by two distinct ligand-induced, tyrosine-phosphorylated docking sites in the interleukin-10 receptor intracellular domain. J Biol Chem 271:27954–27961

    Article  CAS  PubMed  Google Scholar 

  • Williams L, Bradley L, Smith A, Foxwell B (2004) Signal transducer and activator of transcription 3 is the dominant mediator of the anti-inflammatory effects of IL-10 in human macrophages. J Immunol 172:567–576

    Article  CAS  PubMed  Google Scholar 

  • Wolk K, Kunz S, Witte E, Friedrich M, Asadullah K, Sabat R (2004) IL-22 increases the innate immunity of tissues. Immunity 21:241–254

    Article  CAS  PubMed  Google Scholar 

  • Wolk K, Witte E, Wallace E, Döcke WD, Kunz S, Asadullah K et al (2006) IL-22 regulates the expression of genes responsible for antimicrobial defense, cellular differentiation, and mobility in keratinocytes: a potential role in psoriasis. Eur J Immunol 36:1309–1323

    Article  CAS  PubMed  Google Scholar 

  • Xavier RJ, Podolsky DK (2007) Unraveling the pathogenesis of inflammatory bowel disease. Nature 448:427–434

    Article  CAS  PubMed  Google Scholar 

  • Yong PF, Freeman AF, Engelhardt KR, Holland S, Puck JM, Grimbacher B (2012) An update on the hyper-IgE syndromes. Arthritis Res Ther 14:228

    Article  PubMed Central  PubMed  Google Scholar 

  • Zaki MH, Lamkanfi M, Kanneganti TD (2011) The Nlrp3 inflammasome: contributions to intestinal homeostasis. Trends Immunol 32:171–179. doi:10.1016/j.it.2011.02.002

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Centre of Chronic Immunodeficiency, Freiburg, Germany

    Karin R. Engelhardt & Bodo Grimbacher

Authors
  1. Karin R. Engelhardt
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bodo Grimbacher
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bodo Grimbacher .

Editor information

Editors and Affiliations

  1. Deutsches Rheuma-Forschungszentrum Berlin, Berlin, Germany

    Simon Fillatreau

  2. Div. of Immunoregulation, The MRC National Institute for Medical Research, London, United Kingdom

    Anne O'Garra

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Engelhardt, K.R., Grimbacher, B. (2014). IL-10 in Humans: Lessons from the Gut, IL-10/IL-10 Receptor Deficiencies, and IL-10 Polymorphisms. In: Fillatreau, S., O'Garra, A. (eds) Interleukin-10 in Health and Disease. Current Topics in Microbiology and Immunology, vol 380. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-43492-5_1

Download citation

Publish with us

Policies and ethics

Search

Navigation